Repka T, Shalev O, Reddy R, Yuan J, Abrahamov A, Rachmilewitz E A, Low P S, Hebbel R P
Department of Medicine, Hennepin County Medical Center, Minneapolis, MN.
Blood. 1993 Nov 15;82(10):3204-10.
To further define the nature of abnormal iron deposits on the membranes of pathologic red blood cells, we have used sickle cell anemia (HbSS), HbSC, and beta-thalassemic erythrocytes (RBCs) to prepare inside-out membranes (IOM) and insoluble membrane aggregates (AGGs) containing coclustered hemichrome and band 3. Study of IOM from HbSC and thalassemic patients showed that amounts of heme iron and, especially, free iron were much higher in patients who had undergone surgical splenectomy. The membrane AGGs from HbSS and beta-thalassemic RBCs contained much more globin than heme, with this discrepancy being variable from patient to patient. Although these AGGs were enriched (compared with the ghosts from which they were derived) for heme, as expected, less than 10% of total ghost heme was recovered in them. Remarkably, these AGGs also were enriched for nonheme iron, markedly so in some patients. Iron binding studies showed that the association of free iron with these hemichrome/band 3 AGGs is explained by the fact that free iron binds to denatured hemoglobin. These results document that free iron is nonrandomly associated with the membranes of sickle and beta-thalassemic RBCs. Whether this plays a causative role in the premature removal of such cells from the circulation remains to be seen.
为了进一步明确病理性红细胞膜上异常铁沉积的性质，我们使用镰状细胞贫血（HbSS）、HbSC和β地中海贫血红细胞（RBCs）制备了内向外膜（IOM）以及含有共聚集半色素和带3的不溶性膜聚集体（AGGs）。对来自HbSC和地中海贫血患者的IOM研究表明，接受过脾切除术的患者血红素铁尤其是游离铁的含量要高得多。来自HbSS和β地中海贫血RBCs的膜AGGs含有的珠蛋白比血红素多得多，且这种差异在患者之间各不相同。正如预期的那样，尽管这些AGGs（与它们所源自的血影相比）富含血红素，但在其中回收的总血影血红素不到10%。值得注意的是，这些AGGs也富含非血红素铁，在一些患者中尤为明显。铁结合研究表明，游离铁与这些半色素/带3 AGGs的结合可以解释为游离铁与变性血红蛋白结合这一事实。这些结果证明游离铁与镰状和β地中海贫血RBCs的膜存在非随机关联。这是否在这些细胞从循环中过早清除中起因果作用还有待观察。
